This year, we continued to study the role of mismatch repair in regulating the genome-wide mutation rates of yeast cells harboring variant alleles of the major leading and lagging strand enzymes, DNA polymerases epsilon and delta. These studies are being performed in mismatch repair proficient and deficient yeast cells, as reported in the other annual report from this laboratory, 1 Z01 ES065070-27: Structure-Function Studies of DNA Replication Fidelity. They currently include a study published this year on replication in yeast cells deficient in MMR showing the consequences of loss of MMR on reported gene specific mutation rates in cells lacking DNA polymerase epsilon. In addition, we continue to use the new technology called Muver that greatly improves our ability to measure genome-wide mutation rates in MMR-deficient and proficient cells. This technology is very informative regarding the contributions of nucleotide selectivity, proofreading and mismatch repair to genome wide mutation rates for base substitution and insertion-deletion errors. It is being used for studies of genome-wide mutation rates that are currently underway but not yet published.